Using DNA Origami, which involves folding complementary strands of DNA into double helixes, scientists can create small devices with intricate structures that could be injected into the body to deliver medications or do other tasks.
Mice trials show that nanodevices are not harmful in large dosages
The ability to create DNA structures for use in biomedical applications like creating vaccinations or medication delivery systems has been made possible by advances in nanotechnology, but a recent study in mice looks into the safety of the technology.
Scientists can construct a variety of tiny devices with complicated structures that might be implanted in the body to transport medications or carry out other duties using a method called DNA Origami (DO), which involves folding complementary strands of DNA into double helixes repeatedly. However, due to the fact that this technology is still in its infancy, there is disagreement among experts as to whether nanostructures could cause dangerous immune responses or be toxic in other ways in animal systems.
Researchers from The Ohio State University have now made an initial step to provide an answer to that question. The research, which was recently published in the journal Small, discovered that while large quantities of these DNA devices may somewhat impact the immune system, it isn’t marked enough to be harmful. Their results also imply that some medicinal applications may benefit more from different shapes.
“DNA is unbelievable in terms of construction and how it’s able to be manipulated and designed to form nano-robots in a very coordinated manner,” said Christopher Lucas, lead author of the study and a research scientist in mechanical and aerospace engineering at Ohio State. “We believe this technology, which has an incredible amount of potential, can be used to diagnose, treat and prevent disease.”
To test if that can be done safely, Lucas’ team used mice to compare the biodistribution and toxicity of two distinct nanostructures: a flat single-layer 2D Triangle called “Tri,” and a 3D rod-shaped structure that was given the moniker “Horse.” Over a period of 10 days, about 60 female mice were continuously given IV injections of both DO structures. But to really test the safety, the researchers repeatedly dosed the mice at a concentration 10 times greater than in previous studies.
Researchers did see that Tri and Horse created shape-dependent inflammatory responses, but because the response diminished over time, they showed that the immune reaction was relatively harmless in the long run. “It was a modest immune response, but it wasn’t toxic to the animals,” said Lucas. “Understanding that was really key as we move towards preclinical development, and ready the technology for drug delivery applications.”
When the experiment concluded, the team also collected and imaged all of the mice’s major organs, blood and urine to track the device’s final distribution throughout the body. Results showed that both types of nanostructures were internalized by a variety of immune cells, but the amount of DO still left behind differed due to their original concentrations and how long they permeated the body. Because they’re biocompatible, nanostructures also happen to clear the body relatively quickly, Lucas said. And that’s a good thing, especially if scientists want to ensure these devices could be used to target only diseased cells.
But it’s hard to predict the challenges other kinds of nanostructures might run into inside a human or animal body.
“Once you put things into a biological system there’s just so much variability to account for,” said study co-author Carlos Castro, professor of mechanical and aerospace engineering.
As for what’s next, since they’ve shown the technology isn’t toxic to mice, the team wants to start loading the devices up with chemotherapy drugs and begin learning how to use the devices to effectively target cancer cells in animals. “We’re just scratching the surface,” said Castro. “We’re revealing a whole new set of interesting questions that we can dig deeper into.”
Reference: “DNA Origami Nanostructures Elicit Dose-Dependent Immunogenicity and Are Nontoxic up to High Doses In Vivo” by Christopher R. Lucas, Patrick D. Halley, Amjad A. Chowdury, Bonnie K. Harrington, Larry Beaver, Rosa Lapalombella, Amy J. Johnson, Erin K. Hertlein, Mitch A. Phelps, John C. Byrd and Carlos E. Castro, 28 May 2022, Small.
DOI: 10.1002/smll.202108063
The study was funded by the National Institutes of Health.